Atherosclerosis最新文献

{"title":"Epigenetic regulation of vascular smooth muscle cell phenotypes in atherosclerosis.","authors":"Jordi Lambert, Helle F Jørgensen","doi":"10.1016/j.atherosclerosis.2024.119085","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.119085","url":null,"abstract":"<p><p>Vascular smooth muscle cells (VSMCs) in adult arteries maintain substantial phenotypic plasticity, which allows for the reversible cell state changes that enable vascular remodelling and homeostasis. In atherosclerosis, VSMCs dedifferentiate in response to lipid accumulation and inflammation, resulting in loss of their characteristic contractile state. Recent studies showed that individual, pre-existing VSMCs expand clonally and can acquire many different phenotypes in atherosclerotic lesions. The changes in gene expression underlying this phenotypic diversity are mediated by epigenetic modifications which affect transcription factor access and thereby gene expression dynamics. Additionally, epigenetic mechanisms can maintain cellular memory, potentially facilitating reversion to the contractile state. While technological advances have provided some insight, a comprehensive understanding of how VSMC phenotypes are governed in disease remains elusive. Here we review current literature in light of novel insight from studies at single-cell resolution. We also discuss how lessons from epigenetic studies of cellular regulation in other fields could help in translating the potential of targeting VSMC phenotype conversion into novel therapies in cardiovascular disease.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"119085"},"PeriodicalIF":4.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to: \"Unveiling feature importance biases in linear regression: Implications for protein-centric cardiovascular research\".","authors":"Holger Kirsten, Markus Scholz","doi":"10.1016/j.atherosclerosis.2024.119084","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.119084","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"119084"},"PeriodicalIF":4.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Endothelial epoxyeicosatrienoic acid release is intact in aldosterone excess\" [Atherosclerosis 398 (2024) 118591].","authors":"Yao Meng, Aynur Bilyal, Li Chen, Michael Mederos Y Schnitzler, Julien Kocabiyik, Thomas Gudermann, Fabien Riols, Mark Haid, Jair G Marques, Jeannie Horak, Berthold Koletzko, Jing Sun, Felix Beuschlein, Daniel A Heinrich, Christian Adolf, Martin Reincke, Holger Schneider","doi":"10.1016/j.atherosclerosis.2024.119071","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.119071","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"119071"},"PeriodicalIF":4.9,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The low-density lipoprotein receptor: Emerging post-transcriptional regulatory mechanisms.","authors":"Klevis Ndoj, Amber Meurs, Dimitra Papaioannou, Katrine Bjune, Noam Zelcer","doi":"10.1016/j.atherosclerosis.2024.119082","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.119082","url":null,"abstract":"<p><p>Cholesterol is a vital component of cellular membranes and is an essential molecule in mammalian physiology. Yet dysregulation of hepatic cholesterol metabolism and an increase in plasma cholesterol is linked to development of atherosclerotic cardiovascular disease. Maintaining tight regulation of cholesterol homeostasis is therefore essential, elegantly highlighted by the control of hepatic low-density lipoprotein receptor (LDLR) abundance and associated lipoprotein clearance. The LDLR was discovered in the 1970's in the seminal work of Brown and Goldstein. This was followed by the development of statins, which promote hepatic clearance of LDL via the LDLR pathway. The discovery two decades ago of Proprotein Convertase Subtilisin-Kexin Type 9 (PCSK9), a secreted protein that binds to the LDLR ectodomain and promotes its degradation, and the clinical development of PCSK9 inhibitors has ushered an effort to uncover additional mechanisms that govern the function and abundance of the LDLR. In recent years this has led to the identification of novel post-transcriptional and post-translational mechanisms that govern the LDLR. This review focuses on these emerging regulatory mechanisms and specifically discusses: (1) Regulation of the LDLR mRNA by RNA-binding proteins and microRNAs, (2) Ubiquitin-dependent degradation of the LDLR protein by the E3 ubiquitin ligases inducible degrader of the LDLR (IDOL) and GOLIATH (RNF130), (3) Control of the LDLR pathway by the asialoglycoprotein receptor 1 (ASGR1), and (4) The role of LDLR ectodomain shedding mediated by membrane-type 1 matrix metalloprotease (MT1-MMP), Bone morphogenetic protein 1 (BMP1), and γ-secretase. Understanding the contribution of these emerging mechanisms to regulation of the LDLR is important for the development of novel LDLR-focused lipid-lowering strategies.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"119082"},"PeriodicalIF":4.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of genetically predicted levels of circulating blood lipids with coronary artery disease incidence.","authors":"Hasanga D Manikpurage, Jasmin Ricard, Ursula Houessou, Jérôme Bourgault, Eloi Gagnon, Émilie Gobeil, Arnaud Girard, Zhonglin Li, Aida Eslami, Patrick Mathieu, Yohan Bossé, Benoit J Arsenault, Sébastien Thériault","doi":"10.1016/j.atherosclerosis.2024.119083","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.119083","url":null,"abstract":"<p><strong>Background and aims: </strong>Estimating the genetic risk of coronary artery disease (CAD) is now possible by aggregating data from genome-wide association studies (GWAS) into polygenic risk scores (PRS). Combining multiple PRS for specific circulating blood lipids could improve risk prediction. Here, we sought to evaluate the performance of PRS derived from CAD and blood lipids GWAS to predict the incidence of CAD.</p><p><strong>Methods: </strong>This study included individuals aged between 40 and 69 from UK Biobank. We conducted GWAS for blood lipids measured by nuclear magnetic resonance in individuals without lipid-lowering treatments (n = 73,915). Summary statistics were used to derive PRS in the remaining participants (n = 318,051). A PRS_CAD was derived using the CARDIoGRAMplusC4D GWAS. Hazard ratios (HR) for CAD (n = 9017 out of 301,576; median follow-up: 12.6 years) were calculated per standard deviation increase in each PRS. Models' discrimination capacity and goodness-of-fit were evaluated.</p><p><strong>Results: </strong>Out of 30 PRS, 27 were significantly associated with the incidence of CAD (p < 0.0017). The optimal combination of PRS included PRS for CAD, VLDL-C, total cholesterol and triglycerides. Discriminative capacities were significantly increased in the model including PRS_CAD and clinical risk factors (CRF) (C-statistic = 0.778 [0.773-0.782]) compared to the model with CRF only (C-statistic = 0.755 [0.751-0.760], difference = 0.022 [0.020-0.025]). Although the C-statistic remained similar when independent lipids PRS were added to the model with PRS_CAD and CRF (C-statistic = 0.778 [0.773-0.783]), the goodness-of-fit was significantly increased (chi-square test statistic = 20.18, p = 1.56e-04).</p><p><strong>Conclusions: </strong>Although independently associated with CAD incidence, blood lipids PRS provide modest improvement in the predictive performance when added to PRS_CAD.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"119083"},"PeriodicalIF":4.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the complex interplay of PPARα and age in cardiac metabolism: Implications for managing age-related cardiac dysfunctions","authors":"Sina Rashedi,&nbsp;Mohammad Keykhaei","doi":"10.1016/j.atherosclerosis.2024.118627","DOIUrl":"10.1016/j.atherosclerosis.2024.118627","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"399 ","pages":"Article 118627"},"PeriodicalIF":4.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vascular disease and ischemic stroke in patients with atrial fibrillation: Temporal trends and age-related differences","authors":"Konsta Teppo ,&nbsp;Elin Karlsson ,&nbsp;Tuomas Kiviniemi ,&nbsp;Olli Halminen ,&nbsp;Ossi Lehtonen ,&nbsp;Elis Kouki ,&nbsp;Jari Haukka ,&nbsp;Pirjo Mustonen ,&nbsp;Jukka Putaala ,&nbsp;Miika Linna ,&nbsp;Juha Hartikainen ,&nbsp;K.E. Juhani Airaksinen ,&nbsp;Mika Lehto","doi":"10.1016/j.atherosclerosis.2024.118590","DOIUrl":"10.1016/j.atherosclerosis.2024.118590","url":null,"abstract":"<div><h3>Background and aims</h3><div>We examined temporal trends and age-related differences in the prevalence of vascular diseases and in their association with ischemic stroke (IS) risk in patients with atrial fibrillation (AF).</div></div><div><h3>Methods</h3><div>The registry-based FinACAF study covered all patients with AF in Finland during 2007–2018. Incidence rate ratios (IRRs) of IS were computed with Poisson regression, and the interaction of vascular diseases with age and calendar year period was assessed.</div></div><div><h3>Results</h3><div>We identified 229,565 patients (50.0 % female; mean age 72.7 years) with incident AF. The overall prevalence of any vascular disease was 28.6 %, and the prevalence increased from 2007 to 2018, primarily among patients over 75 years. Overall, 5909 (2.6 %) patients experienced IS within the first year after AF diagnosis. Crude IS rate decreased continuously during the study period in both patients with and without vascular diseases, with the rates remaining consistently higher in patients with vascular diseases. Vascular diseases were independently associated with higher IS incidence among patients under 65 years (adjusted IRR with 95 % confidence interval 1.35 (1.10–1.66)), while among older patients, only peripheral artery disease was associated with IS, and other vascular conditions had no association with IS. No interactions between the calendar year period and vascular diseases with IS rate were observed.</div></div><div><h3>Conclusions</h3><div>The association between vascular diseases and IS has remained stable over time and vascular diseases were independently associated with higher incidence of IS particularly in patients with AF under the age of 65.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"399 ","pages":"Article 118590"},"PeriodicalIF":4.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The age-dependent development of abnormal cardiac metabolism in the peroxisome proliferator-activated receptor α-knockout mouse","authors":"Michael S. Dodd ,&nbsp;Lucy Ambrose ,&nbsp;Vicky Ball ,&nbsp;Kieran Clarke ,&nbsp;Carolyn A. Carr ,&nbsp;Damian J. Tyler","doi":"10.1016/j.atherosclerosis.2024.118599","DOIUrl":"10.1016/j.atherosclerosis.2024.118599","url":null,"abstract":"<div><h3>Background and aims</h3><div>Peroxisome proliferator-activated receptor α (PPARα) is crucial for regulating cardiac β-oxidation in the heart, liver, and kidney. Ageing can induce cardiac metabolic alterations, but the role of PPARα has not been extensively characterised. The aim of this research was to investigate the role of PPARα in the aged heart.</div></div><div><h3>Methods</h3><div>Hyperpolarized [1–¹³C]pyruvate was used to evaluate <em>in vivo</em> cardiac carbohydrate metabolism in fed and fasted young (3 months) and old (20–22 months) PPARα knockout (KO) mice <em>versus</em> controls. Cine MRI assessed cardiac structural and functional changes. Cardiac tissue analysis included qRT-PCR and Western blotting for <em>Ppar</em>α<em>,</em> medium chain acyl-CoA dehydrenase (MCAD), uncoupling protein (UCP) 3, glucose transporter (GLUT) 4 and PDH kinase (PDK) 1,2, and 4 expression.</div></div><div><h3>Results</h3><div>PPARα-KO hearts from both young and old mice showed significantly reduced Pparα mRNA and a 58–59 % decrease in MCAD protein levels compared to controls. Cardiac PDH flux was similar in young control and PPARα-KO mice but 96 % higher in old PPARα-KO mice. Differences between genotypes were consistent in fed and fasted states, with reduced PDH flux when fasted. Increased PDH flux was accompanied by a 179 % rise in myocardial GLUT4 protein. No differences in PDK 1, 2, or 4 protein levels were observed between fed groups, indicating the increased PDH flux in aged PPARα-KO mice was not due to changes in PDH phosphorylation.</div></div><div><h3>Conclusions</h3><div>Aged PPARα-KO mice demonstrated higher cardiac PDH flux compared to controls, facilitated by increased myocardial GLUT4 protein levels, leading to enhanced glucose uptake and glycolysis.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"399 ","pages":"Article 118599"},"PeriodicalIF":4.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Very short-term effects of a single dose of a proprotein convertase subtilisin/kexin 9 inhibitor before percutaneous coronary intervention: A single-arm study","authors":"Tatsuhiro Kataoka ,&nbsp;Tetsuji Morishita ,&nbsp;Hiroyasu Uzui ,&nbsp;Yusuke Sato ,&nbsp;Tomohiro Shimizu ,&nbsp;Machiko Miyoshi ,&nbsp;Junya Yamaguchi ,&nbsp;Yuichiro Shiomi ,&nbsp;Hiroyuki Ikeda ,&nbsp;Naoto Tama ,&nbsp;Kanae Hasegawa ,&nbsp;Kentaro Ishida ,&nbsp;Hiroshi Tada","doi":"10.1016/j.atherosclerosis.2024.118581","DOIUrl":"10.1016/j.atherosclerosis.2024.118581","url":null,"abstract":"<div><h3>Background and aims</h3><div>The short-term (within 6 weeks) effects of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors on lipid plaques have not been adequately evaluated. We aimed to investigate whether a single dose of a PCSK9 inhibitor before percutaneous coronary intervention (PCI) could reduce the abundance of lipid-core plaques identified via near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) at target lesions within a very short period.</div></div><div><h3>Methods</h3><div>This prospective, single-arm, single-center interventional study enrolled 27 consecutive patients with coronary artery disease. These patients underwent NIRS-IVUS during coronary angiography and repeat NIRS-IVUS during PCI performed between 2 and 6 weeks after the single-dose administration of 420 mg evolocumab. Changes in lesion lipid-core burden index (LCBI) and maximal LCBI over any 4-mm segment (max-LCBI_4mm) were assessed using NIRS at the target lesions, along with lipid profile.</div></div><div><h3>Results</h3><div>The max-LCBI_4mm significantly decreased from 387 before PCSK9 inhibitor administration to 315 after its administration (interquartile range [IQR]: 268–572 and 221–488, respectively; <em>p</em> = 0.02) within a very short period. The lesion LCBI also decreased from 161 to 117 (IQR: 105–263 and 65–226, respectively; <em>p</em> = 0.02). No significant changes were observed in the minimum lumen area and diameter. After PCSK9 inhibitor administration, low-density lipoprotein (LDL) cholesterol (<em>p</em> &lt; 0.001), lipoprotein(a) (<em>p</em> = 0.001), and malondialdehyde-modified LDL (<em>p</em> &lt; 0.001) levels decreased compared with those before its administration.</div></div><div><h3>Conclusions</h3><div>A single dose of the PCSK9 inhibitor administered before PCI reduced the abundance of lipid-core plaques identified via NIRS-IVUS at target lesions within a very short period of 2–6 weeks.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"399 ","pages":"Article 118581"},"PeriodicalIF":4.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age drives the impact of vascular disease on ischemic stroke in patients with atrial fibrillation: Role of hypertension and prediabetes","authors":"Pasquale Mone,&nbsp;Florindo D'Onofrio,&nbsp;Tommaso Dazzetti,&nbsp;Thais Luma De Oliveira Roza,&nbsp;Germano Guerra,&nbsp;Gaetano Santulli","doi":"10.1016/j.atherosclerosis.2024.118619","DOIUrl":"10.1016/j.atherosclerosis.2024.118619","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"399 ","pages":"Article 118619"},"PeriodicalIF":4.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}